As indicated in U.S. Pat. No. 4,189,591, 4-methyl-5-hydroxymethylimidazole was discovered by WINDAUS in 1909 and was made by the reaction of formaldehyde with 4-methylimidazole. This product is a suitable intermediate for making Cimetidine.
U.S. Pat. No. 4,189,591 was purportedly directed to making this product by an improved process. The improved process was purportedly carried out in aqueous reaction media. The Patent specifies the reaction must be carried out under closely controlled conditions (column 1, lines 31-32). The patent also specifies that when the water is replaced by methanol, only trace amounts of 4-methyl-5-hydroxymethyl-imidazole was found in the reaction mixture (column 2, line 67-column 3, line 1). According to the patent, "the other common solvents are no better . . ." (column 3, lines 1-2).
With each of the processes, there are deficiences relating to reactants, conditions of reactions and yields.
In U.S. Pat. No. 4,275,216, a process is provided by which 4(5)-hydroxymethyl-5(4)-lower- alkyl imidazoles may be manufactured. The process reacts 5(4)-lower alkyl imidazole with formaldehyde in the presence of a strong base (for example, a mineral base such as sodium hydroxide, tertiary amine, quarternary ammonium hydroxide and alkaline metal alcoholates) and at a reaction temperature of 60-95.degree. C.
It is therefore an object of this invention to provide an improved process which is easier to use and more environmentally friendly providing the ability to separate easily and recover non-reactant materials (such as the solvent and mild base) used in the process.
Further and other objects of the invention will be realized by those skilled in the art from the following Summary of Invention and Detailed Description of Embodiments Thereof.